Abstract
The cytokine interleukin-6 (IL-6), a key mediator of immune and acute phase responses of the liver, has also been implicated in uterine functions. Estrogens are potent repressors of IL-6 production by uterine stromal cells. In the endometrial adenocarcinoma cell line Ishikawa, phorbol ester-induced activation of the IL-6 promoter was inhibited to basal levels by 17 beta-estradiol (E2) in a wild-type receptor-dependent fashion. Although tamoxifen has been shown to have estrogenic effects on the endometrium, it did not inhibit induction of the IL-6 promoter. We previously showed that inhibition of IL-6 gene expression by E2 does not involve high-affinity binding of the estrogen receptor (ER) to IL-6 DNA. We now report that the ER can directly interact with the transcription factors NF-IL6 and NF-kappa B and can inhibit their ability to bind DNA which might be the molecular basis for repression of IL-6 gene expression by estrogens.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma
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CCAAT-Enhancer-Binding Proteins
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DNA-Binding Proteins / antagonists & inhibitors*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Drug Combinations
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Endometrial Neoplasms
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Estradiol / pharmacology*
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Female
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Gene Expression Regulation / drug effects*
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Humans
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Interleukin-6 / genetics*
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Nuclear Proteins / antagonists & inhibitors*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Promoter Regions, Genetic / drug effects
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Receptors, Estrogen / chemistry
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Receptors, Estrogen / physiology*
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Structure-Activity Relationship
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Tamoxifen / pharmacology
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Tetradecanoylphorbol Acetate / pharmacology
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Tumor Cells, Cultured
Substances
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CCAAT-Enhancer-Binding Proteins
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DNA-Binding Proteins
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Drug Combinations
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Interleukin-6
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NF-kappa B
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Nuclear Proteins
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Receptors, Estrogen
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Tamoxifen
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Estradiol
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Tetradecanoylphorbol Acetate